Journal of Organic Chemistry 2006-06-09

Synthetic transformation of ptychantin into forskolin and 1,9-dideoxyforskolin.

Hisahiro Hagiwara, Fumihide Takeuchi, Masaru Kudou, Takashi Hoshi, Toshio Suzuki, Toshihiro Hashimoto, Yoshinori Asakawa

Index: J. Org. Chem. 71(12) , 4619-24, (2006)

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Abstract

Forskolin (1), a highly oxygenated labdane diterpenoid and an activator of adenylate cyclase, has been synthesized in 12 steps and 12% overall yield from ptychantin A (4), which has been isolated from liverwort Ptychanthus striatus in good yield. The 1alpha-hydroxy group was furnished by stereoselective reduction of the corresponding carbonyl group by sodium in t-BuOH. The 9alpha-hydroxy group was introduced stereoselectively by epoxidation of delta(9.11)-enolether. 1,9-Dideoxyforskolin (2), an inhibitor of glucose transporter, has been synthesized in 8 steps and 37% overall yield. The hydroxy group at C-1 was removed by solid-state thicarbonylimidazolation and subsequent radical cleavage.